title: SNX18 tubulates recycling endosomes for autophagosome biogenesis.
abstract: The role of membrane remodeling and phosphoinositide-binding proteins in autophagy remains elusive. PX domain proteins bind phosphoinositides and participate in membrane remodeling and trafficking events and we therefore hypothesized that one or several PX domain proteins are involved in autophagy. Indeed, the PX-BAR protein SNX18 was identified as a positive regulator of autophagosome formation using an image-based siRNA screen. We show that SNX18 interacts with ATG16L1 and LC3, and functions downstream of ATG14 and the class III PtdIns3K complex in autophagosome formation. SNX18 facilitates recruitment of ATG16L1 to perinuclear recycling endosomes, and its overexpression leads to tubulation of ATG16L1- and LC3-positive membranes. We propose that SNX18 promotes LC3 lipidation and tubulation of recycling endosomes to provide membrane for phagophore expansion.
authors.affiliation: Institute of Basic Medical Sciences; University of Oslo; Oslo, Norway.
authors.forename: Helene
authors.initials: H
authors.lastname: Knævelsrud
authors.affiliation: Department of Medical Biochemistry and Biophysics; Umeå University; Umeå, Sweden.
authors.forename: Sven R
authors.initials: SR
authors.lastname: Carlsson
authors.affiliation: Institute of Basic Medical Sciences; University of Oslo; Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Simonsen
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D010588:Phagosomes / Q000378:metabolism*; D058305:Sorting Nexins / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C530791:SNX18 protein, human; D058305:Sorting Nexins
keywords: ATG16L1; PX-BAR protein; RAB11; SNX18; autophagosome formation; recycling endosomes